Inline dilution and autocalibration for icp-ms speciation analysis

ABSTRACT

Systems and methods for speciation of chemicals of interest with inline and automatic dilution or addition of other fluids prior to or following speciation with subsequent analysis by ICP instruments are described. A system embodiment includes, but is not limited to, a first valve having a first valve configuration to receive a sample into a holding loop coupled to the first valve and a second valve configuration to transfer the sample from the holding loop; and a second valve having a first valve configuration configured to receive the sample from the first valve and direct the sample to a speciation column to separate one or more species of the sample, the second valve further including a fluid addition port configured to receive a fluid into the second valve to mix with the sample after the sample exits the speciation column.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims the benefit of 35 U.S.C. § 119(e) of U.S.Provisional Application Ser. No. 62/627,946, filed Feb. 8, 2018, andtitled “INLINE DILUTION AND AUTOCALIBRATION FOR ICP-MS SPECIATIONANALYSIS.” U.S. Provisional Application Ser. No. 62/627,946 is hereinincorporated by reference in its entirety.

BACKGROUND

Spectrometry refers to the measurement of radiation intensity as afunction of wavelength to identify component parts of materials.Inductively Coupled Plasma (ICP) spectrometry is an analysis techniquecommonly used for the determination of trace element concentrations andisotope ratios in liquid samples. For example, in the semiconductorindustry, ICP spectrometry can be used to determine metal concentrationsin samples. ICP spectrometry employs electromagnetically generatedpartially ionized argon plasma which reaches a temperature ofapproximately 7,000K. When a sample is introduced to the plasma, thehigh temperature causes sample atoms to become ionized or emit light.Since each chemical element produces a characteristic mass or emissionspectrum, measuring the spectra of the emitted mass or light allows thedetermination of the elemental composition of the original sample. Thesample to be analyzed is often provided in a sample mixture.

Sample introduction systems may be employed to introduce liquid samplesinto the ICP spectrometry instrumentation (e.g., an Inductively CoupledPlasma Mass Spectrometer (ICP/ICP-MS), an Inductively Coupled PlasmaAtomic Emission Spectrometer (ICP-AES), or the like) for analysis. Forexample, a sample introduction system may withdraw an aliquot of aliquid sample from a container and thereafter transport the aliquot to anebulizer that converts the aliquot into a polydisperse aerosol suitablefor ionization in plasma by the ICP spectrometry instrumentation. Theaerosol is then sorted in a spray chamber to remove the larger aerosolparticles. Upon leaving the spray chamber, the aerosol is introducedinto the plasma by a plasma torch assembly of the ICP-MS or ICP-AESinstruments for analysis.

DRAWINGS

The detailed description is described with reference to the accompanyingfigures. In the figures, the use of the same reference numbers indifferent instances in the description and the figures may indicatesimilar or identical items.

FIG. 1 is an illustration of an ICP spectrometry system for inlinedilution of samples for speciation analysis in accordance with exampleimplementations of the present disclosure.

FIG. 2 is a block diagram illustrating a computing system forcontrolling a system for inline dilution of samples for speciationanalysis by an ICP spectrometry system, such as the system shown in FIG.1.

FIGS. 3A through 3C are schematic illustrations of a valve systemincluding a speciation bypass valve for a system for inline dilution ofsamples for speciation analysis by an ICP spectrometry system.

FIG. 4A is a chart showing detected arsenic over time for variousdilutions of apple juice samples.

FIG. 4B is a chart showing detected arsenic over time for variousdilutions of rice flour samples.

FIG. 5 is a calibration chromatogram overlay via auto-calibration of asingle mixed standard and a calibration blank.

FIG. 6 is a chart for calibration curves for five of the major arsenicspecies resulting from auto-calibration.

FIG. 7A is a chart showing an arsenic species detection over time forautomated inline dilution.

FIG. 7B is a chart showing an arsenic species detection over time formanual dilution with deionized water.

FIG. 7C is a chart showing an arsenic species detection over time formanual dilution with mobile phase.

FIG. 8A is a chart illustrating effects of manual dilution on measuredarsenate concentrations between various samples.

FIG. 8B is a chart illustrating effects of manual dilution on measuredarsenic species concentrations between various samples.

FIG. 9 is a chart illustrating spike recovery for five of the majorarsenic species for apple juice and rice flour extraction matrices.

FIGS. 10A through 10C are schematic illustrations of a valve system inspeciation mode for speciation analysis by an ICP spectrometry system.

FIG. 10D is a chart illustrating a chart showing an arsenic speciesdetection over time with the valve system in speciation mode.

FIGS. 11A through 11C are schematic illustrations of the valve system ofFIGS. 10A through 10C in a total metals mode for analysis the an ICPspectrometry system.

FIG. 11D is a chart illustrating a chart showing total arsenic detectionover time with the valve system in total metals mode.

FIGS. 12A and 12B are schematic illustrations of a valve system forspeciation of samples for speciation analysis in accordance with exampleimplementations of the present disclosure.

FIG. 13 is an illustration of an ICP spectrometry system for speciationof samples and subsequent fluid addition for speciation analysis inaccordance with example implementations of the present disclosure.

FIG. 14 is a table illustrating syringe pump operating conditions duringspeciation of a sample in accordance with example implementations of thepresent disclosure.

DETAILED DESCRIPTION

Referring to FIGS. 1-14, systems and methods for speciation of chemicalsof interest with inline and automatic dilution or addition of otherfluids prior to or following speciation with subsequent analysis by ICPinstruments are described. Analysis of the various species of an elementis an important aspect of sample analysis, particularly where an assayof the particular element alone may not provide all relevant informationassociated with that element. For instance, differing species of anelement can have remarkably different toxicity levels, where knowledgeof an amount of the element in general does not provide an indication asto the toxicity of that element. For example, one species of chromium(e.g., Cr(III)) can provide nutritive benefits, whereas another speciesof chromium (e.g., Cr(VI)) is toxic to humans as a carcinogen. Asanother example, some organic arsenic species (e.g., arsenobetaine(AsB)) can be relatively non-toxic or have low toxicity, whereasinorganic arsenic species (e.g., arsenite (As(III)), arsenate (As(V)))are highly toxic. As a further example, organic mercury (methylmercury)is more toxic than the inorganic form (Hg II).

ICP-MS can be utilized to determine the presence of certain chemicalelements, even at extremely low concentrations, however ICP-MS does nottypically distinguish between differing species of the chemicalelements. One procedure to differentiate different species of an elementincludes using a separation column (e.g., a speciation column) toseparate the differing species from a fluid stream over time, where thespecies can be measured at the ICP-MS as peaks of the element at varioustimes as the species are separated. The peaks can be influenced by thematrix compositions of the various materials sampled, which can includefood materials (e.g., apple juice, rice flour, etc.). For example, theshape of the peak, the times at which the peaks arise, etc., can beinfluenced by the matrix compositions of the sample. To avoid largedeviations in the sample analysis, the samples can be diluted to lowerconcentrations to minimize the effects of the matrix on the sampleanalysis, such as by avoiding substantial changes to the chemistry ofthe particular speciation column. However, attempting to pre-dilute thesample can cause species of the particular element of interest toconvert to a different species of that element (“speciesinterconversion”), resulting in an erroneous analysis of the amount ofspecies by the ICP-MS. For example, it has been determined that organicspecies of arsenic (e.g., arsenobetaine (AsB), dimethylarsinic acid(DMA), and monomethylarsonic acid (MMA)) can covert to inorganic speciesof arsenic (e.g., arsenate (As(V))) when manually pre-diluted in asample vial (e.g., a sample vial accessible by an autosampler). Thus,while the total amount of the chemical element of interest would bemeasured the same by the ICP-MS, the amount of the individual species ofthe chemical element of interest would differ due to the conversion ofone species of the chemical element to another species prior toanalysis. Further, while high pressure liquid chromatography (HPLC) canbe utilized for speciation, such HPLC systems typically include metalcomponents or parts to facilitate the required high pressures of thesystems, which can pose a contamination risk for detecting lowconcentrations of chemical elements.

Accordingly, the present disclosure is directed to systems and methodsfor speciation of chemicals of interest with inline and automaticdilution or addition of other fluids prior to or following speciationwith subsequent analysis by ICP instruments. A system embodimentincludes, but is not limited to, a first valve, the first valve having afirst valve configuration to receive a sample into a holding loopcoupled to the first valve and a second valve configuration to transferthe sample from the holding loop out of the first valve throughoperation of a pump; and a second valve coupled to the first valve, thesecond valve having a first valve configuration configured to receivethe sample from the first valve and direct the sample to a speciationcolumn to separate one or more species of the sample from respectiveother species of the sample, the second valve further including a fluidaddition port configured to receive a fluid into the second valve to mixwith the sample after the sample exits the speciation column, the secondvalve having a second valve configuration configured to receive thesample from the first valve and bypass the speciation column whiletransferring the sample out of the second valve.

By providing inline and automatic dilution, chemicals can be speciatedand analyzed in real time, rather than pre-diluting each sample (e.g.,in a sample vial) and allowing the samples to wait for an autosampler toremove the pre-diluted sample for speciation and analysis (which canprovide time for the species to convert to a different species of thechemical of interest). While specific examples are provided hereindirected to arsenic and arsenic species, the systems and methods forautomatic inline dilution are not limited to arsenic and arsenic speciesand can encompass any and all solutions that may not be stable in adiluted form for any period of time after preparation. Examples includenot only other elements, but also immiscible or partially misciblesolutions, such as oils, etc. The systems described herein can operateat low pressures via syringe pumps (e.g., as opposed to peristalticpumps) in a clean system to provide chemical assays with high accuracy.For example, in an implementation, the systems described herein includeno metallic component in contact with the sample fluid, which canprevent a risk of metallic contamination associated with such contact.Further, introduction of fluids following separation of the chemicalspecies with a separation column allows for post-column dilution (e.g.,to provide favorable column separation conditions, while avoidingsaturation of ICP-MS cones), introduction of standards for intermittentinternal checks, continuous operation stability checks, etc.,introduction of chemicals for derivatization (e.g., to form detectablecomplexes with otherwise difficult-to-detect species), and the like.

In the following discussion, example implementations of techniques forproviding speciation of chemicals of interest with inline and automaticdilution or addition of other fluids prior to or following speciationwith subsequent analysis by ICP instruments are presented.

EXAMPLE IMPLEMENTATIONS

FIG. 1 illustrates a system 100 for providing inline and automaticdilution of chemicals of interest for speciation and subsequent analysisby ICP-MS in an example implementation. As shown, the system 100generally includes a sampling device 102 (e.g., autosampler), a valvesystem 104, and a speciation column 106 in fluid communication with anICP torch assembly 108. The valve system 104 includes one or more valvesswitchable between a plurality of positions to facilitate flow ofvarious fluids (e.g., sample fluids, carrier fluids, diluent fluids,internal standard fluids, eluent fluids, rinse fluids, etc.) through thesystem 100. In an implementation, the valve system 104 includes at leasta first valve 110, a second valve 112, and a third valve 114. Forexample, one or more of the first valve 110, the second valve 112, andthe third valve 114 can be rotary valves switchable between valveconfigurations to facilitate different flow paths for fluids flowingthrough the respective valve between different valve configurations. Thefirst valve 110 is coupled to the sampling device 102 to receive asample 103 and to hold the received sample 103, such as in a holdingloop 116. As used herein, the term “loop” can refer to a length of fluidline (e.g. tube) suitable to hold a desired volume of fluid for a timeperiod prior to pushing or pulling the fluid from the fluid line to beused elsewhere within the system, where the fluid line can be in acoiled configuration (e.g., shown in FIG. 1), a straight configuration,or other configuration. For example, in an implementation the firstvalve 110 is switchable between at least two configurations, wherein ina first valve configuration, the first valve 110 provides a flow path toreceive the sample 103 from the sampling device 102 and direct thereceived sample 103 to the holding loop 116. The first valve 110 is alsocoupled to a pump system 118 configured to supply to the first valve 110one or more internal standards, diluents, carriers, and rinse solutions.In an implementation, the pump system 118 includes a plurality ofsyringe pumps shown as 118 a, 118 b, 118 c, and 118 d that arecontrolled to move each respective syringe at a particular rate tocreate desired dilutions of the sample and/or standard additions to thesample at the first valve 110. For example, the first valve 110 canswitch to a second valve configuration having a flow path to receive acarrier fluid from the carrier syringe pump 118 b, a diluent fluid fromthe diluent syringe pump 118 c, and a standard fluid from the standardsyringe pump 118 d, whereby the fluids provide inline dilution of thesample 103 and deliver the diluted sample from the first valve 110 tothe second valve 112. While four syringe pumps are shown in FIG. 1, itis can be appreciated that fewer than four syringe pumps or greater thanfour syringe pumps could also be utilized. In an implementation, each ofthe syringe pumps of the pump system 118 (e.g., syringe pumps 118 a, 118b, 118 c, and 118 d) can operate at a particular injection rate toprovide the controlled dilution or the controlled standard addition atthe first valve 110. As an example, the following table 1 illustratesflow rates for standard (e.g., via syringe pump 118 d) and diluent(e.g., via syringe pump 118 c) to provide various inline dilutionfactors (e.g., from the first valve 110) for automatic preparation ofvarious calibration curves. In an implementation the diluent, standard,and/or sample can be mixed via a mixing portion of the first valve 110,where the mixing portion can include one or more of a mixing port 124, amixing channel 126, and a fluid transfer line 128 coupled between thefirst valve 110 and the second valve 112, to bring the diluent,standard, and/or sample together for mixing. The inline dilution factorscan be prepared for individual species of an element (e.g., Cr(III) andCr(VI); arsenobetaine (AsB), dimethylarsinic acid (DMA),monomethylarsonic acid (MMA) arsenite (As(III)), and arsenate (As(V));etc.), such as to provide individualized calibration curves for eachspecies under analysis.

TABLE 1 Calibration Curve Flow Rates Inline Diluent Flow Total FlowStandard Dilution Standard Flow Rate Rate Concentration Position FactorRate (μL/min) (μL/min) (μL/min) (100 ppt) 1 (Blank) 200x  50 9950 100000 2 (Species A) 20x  500 9500 10000 5 2 (Species A) 10x  1000 9000 1000010 2 (Species A)   6.6x 1500 8500 10000 15 2 (Species A) 5x 2000 800010000 20 2 (Species A) 4x 2500 7500 10000 25 2 (Species A) 2x 5000 500010000 50

In an implementation, the inline dilution factors, introduction ofstandards solutions, and introduction of other fluids are facilitatedthrough automatic control of one or more components of the system 100.For example, electromechanical devices (e.g., electrical motors, servos,actuators, or the like) may be coupled with or embedded within the valvesystem 104 (e.g., the first valve 110, the second valve 112, the thirdvalve 114, etc.), and/or the pump system 118 (e.g., syringe pumps 118 a,118 b, 118 c, and 118 d, etc.), and/or another pump/valve to facilitateautomated operation via control logic embedded within or externallydriving the system 100. The electromechanical devices can be configuredto cause the plurality of valves to direct fluid flows from syringepumps 118 a, 118 b, 118 c, and 118 d, and from other syringes, flowpaths, eluent sources, etc., according to one or more modes ofoperation. As shown in FIG. 2, the auto-sampling system 100 may becontrolled by a computing system 150 having a processor 152 configuredto execute computer readable program instructions 154 (i.e., the controllogic) from a non-transitory carrier medium 156 (e.g., storage mediumsuch as a flash drive, hard disk drive, solid-state disk drive, SD card,optical disk, or the like). The computing system 150 can be connected tovarious components of the system 100, either by direct connection, orthrough one or more network connections 158 (e.g., local area networking(LAN), wireless area networking (WAN or WLAN), one or more hubconnections (e.g., USB hubs), and so forth). For example, the computingsystem 150 can be communicatively coupled to the sampling device 102,the valve system 104, the pump system 118, components thereof, any ofthe various pumps or valves provided herein, or combinations thereof.The program instructions 154, when executing by processor 152, can causethe computing system 150 to control the auto-sampling system 100 (e.g.,control the pumps and valves) according to one or more modes ofoperation (e.g., automatic calibration curve(s), sample collection,sample dilution, speciation, speciation bypass, post-speciation fluidaddition, etc.), as described herein. In an implementation, the programinstructions 154 form at least a portion of software programs forexecution by the processor 152.

The processor 152 provides processing functionality for the computingsystem 150 and may include any number of processors, micro-controllers,or other processing systems, and resident or external memory for storingdata and other information accessed or generated by the computing system150. The processor 152 is not limited by the materials from which it isformed or the processing mechanisms employed therein and, as such, maybe implemented via semiconductor(s) and/or transistors (e.g., electronicintegrated circuits (ICs)), and so forth.

The non-transitory carrier medium 156 is an example of device-readablestorage media that provides storage functionality to store various dataassociated with the operation of the computing system 150, such as asoftware program, code segments, or program instructions 154, or otherdata to instruct the processor 152 and other elements of the computingsystem 150 to perform the techniques described herein. Although a singlecarrier medium 156 is shown in FIG. 2, a wide variety of types andcombinations of memory may be employed. The carrier medium 156 may beintegral with the processor, stand-alone memory, or a combination ofboth. The carrier medium 156 may include, for example, removable andnon-removable memory elements such as RAM, ROM, Flash (e.g., SD Card,mini-SD card, micro-SD Card), magnetic, optical, USB memory devices, andso forth. In embodiments of the computing system 150, the carrier medium156 may include removable ICC (Integrated Circuit Card) memory such asprovided by SIM (Subscriber Identity Module) cards, USIM (UniversalSubscriber Identity Module) cards, UICC (Universal Integrated CircuitCards), and so on.

The computing system 150 can include one or more displays to displayinformation to a user of the computing system 150. In embodiments, thedisplay may comprise a CRT (Cathode Ray Tube) display, an LED (LightEmitting Diode) display, an OLED (Organic LED) display, an LCD (LiquidCrystal Diode) display, a TFT (Thin Film Transistor) LCD display, an LEP(Light Emitting Polymer) or PLED (Polymer Light Emitting Diode) display,and so forth, configured to display text and/or graphical informationsuch as a graphical user interface. The display may be backlit via abacklight such that it may be viewed in the dark or other low-lightenvironments. The display may be provided with a touch screen to receiveinput (e.g., data, commands, etc.) from a user. For example, a user mayoperate the computing system 150 by touching the touch screen and/or byperforming gestures on the touch screen. In some embodiments, the touchscreen may be a capacitive touch screen, a resistive touch screen, aninfrared touch screen, combinations thereof, and the like. The computingsystem 150 may further include one or more input/output (I/O) devices(e.g., a keypad, buttons, a wireless input device, a thumbwheel inputdevice, a trackstick input device, and so on). The I/O devices mayinclude one or more audio I/O devices, such as a microphone, speakers,and so on.

The computing system 150 may also include a communication modulerepresentative of communication functionality to permit computing deviceto send/receive data between different devices (e.g.,components/peripherals) and/or over the one or more networks 158. Thecommunication module may be representative of a variety of communicationcomponents and functionality including, but not necessarily limited to:a browser; a transmitter and/or receiver; data ports; softwareinterfaces and drivers; networking interfaces; data processingcomponents; and so forth.

The one or more networks 158 are representative of a variety ofdifferent communication pathways and network connections which may beemployed, individually or in combinations, to communicate among thecomponents of the inline dilution and autocalibration system environment(e.g., system 100). Thus, the one or more networks 158 may berepresentative of communication pathways achieved using a single networkor multiple networks. Further, the one or more networks 158 arerepresentative of a variety of different types of networks andconnections that are contemplated including, but not necessarily limitedto: the Internet; an intranet; a Personal Area Network (PAN); a LocalArea Network (LAN) (e.g., Ethernet); a Wide Area Network (WAN); asatellite network; a cellular network; a mobile data network; wiredand/or wireless connections; and so forth. Examples of wireless networksinclude, but are not necessarily limited to: networks configured forcommunications according to: one or more standard of the Institute ofElectrical and Electronics Engineers (IEEE), such as 802.11 or 802.16(Wi-Max) standards; Wi-Fi standards promulgated by the Wi-Fi Alliance;Bluetooth standards promulgated by the Bluetooth Special Interest Group;and so on. Wired communications are also contemplated such as throughUniversal Serial Bus (USB), Ethernet, serial connections, and so forth.

The computing system 150 is described as including a user interface,which is storable in memory (e.g., the carrier medium 156) andexecutable by the processor 152. The user interface is representative offunctionality to control the display of information and data to the userof the computing system 150 via the display. In some implementations,the display may not be integrated into the computing system 150 and mayinstead be connected externally using universal serial bus (USB),Ethernet, serial connections, and so forth. The user interface mayprovide functionality to allow the user to interact with one or moreapplications of the computing system 150 by providing inputs (e.g.,sample identities, desired dilution factors, standard identities, eluentidentities/locations, fluid addition flow rates, etc.) via the touchscreen and/or the I/O devices. For example, the user interface may causean application programming interface (API) to be generated to exposefunctionality to an online dilution control program to configure theapplication for display by the display or in combination with anotherdisplay. In embodiments, the API may further expose functionality toconfigure an inline dilution control program to allow the user tointeract with an application by providing inputs via the touch screenand/or the I/O devices to provide desired dilution factors for analysis.

The inline dilution control program may comprise software, which isstorable in memory (e.g., the carrier medium 156) and executable by theprocessor 152, to perform a specific operation or group of operations tofurnish functionality to the computing system 150. The inline dilutioncontrol program provides functionality to control the dilution of, forexample, an internal standard and/or the samples from the samplingdevice 102. For example, the inline dilution control program may controlamounts of the carrier and/or the diluent that are supplied by pumps ofthe pump system 118 (e.g., to the first valve 110 for mixing with thesample 103 carried from the holding loop 116).

In implementations, the user interface may include a browser (e.g., forimplementing functionality of the inline dilution control module). Thebrowser enables the computing device to display and interact withcontent such as a webpage within the World Wide Web, a webpage providedby a web server in a private network, and so forth. The browser may beconfigured in a variety of ways. For example, the browser may beconfigured as an inline dilution control program accessed by the userinterface. The browser may be a web browser suitable for use by a fullresource device with substantial memory and processor resources (e.g., asmart phone, a personal digital assistant (PDA), etc.).

Generally, any of the functions described herein can be implementedusing software, firmware, hardware (e.g., fixed logic circuitry), manualprocessing, or a combination of these implementations. The terms“program” and “functionality” as used herein generally representsoftware, firmware, hardware, or a combination thereof. Thecommunication between modules in the system 100, for example, can bewired, wireless, or some combination thereof. In the case of a softwareimplementation, for instance, a program may represent executableinstructions that perform specified tasks when executed on a processor,such as the processor 152 described herein. The program code can bestored in one or more device-readable storage media, an example of whichis the non-transitory carrier medium 156 associated with the computingsystem 150.

Referring again to FIG. 1, the second valve 112 is shown coupled betweenthe first valve 110 and the third valve 114 and is configured to receivefluids from the first valve 110 and the third valve 114. For example, inan implementation the second valve 112 is switchable between at leasttwo configurations, wherein in a first valve configuration, the secondvalve 112 provides a flow path to receive the diluted sample from thefirst valve 110 and direct the diluted sample to a sample holding loop120. The second valve 112 is also coupled to the speciation column 106,such as to introduce fluids received from the first valve 110 and thethird valve 114 to the speciation column 106. For example, the secondvalve 112 can switch to a second valve configuration to provide a flowpath that can introduce one or more of the sample, diluted samplesolution, standard solution, diluted standard solution, or the like fromthe holding loop 120 (or directly from the first valve 110) to thespeciation column 106 to separate the various species of the chemical ofinterest. In an implementation, once the sample or diluted sample hasbeen introduced to the speciation column 106, the second valve 112 canintroduce one or more eluents received from the third valve 114 fortransferring the species of interest from the speciation column 106 tothe ICP torch assembly 108 for ICP-MS analysis.

In an implementation, the system 100 can alternate between speciationanalysis of the sample 103 and a total metals analysis of the samplewithout speciation. For example, referring to FIGS. 3A-3C, the system100 can include a speciation bypass valve 300 coupled between the secondvalve 112 and the speciation column 106. The speciation bypass valve 300is switchable between at least two configurations, with at least aspeciation configuration 300A (shown in FIG. 3B) and a speciation bypassconfiguration 300B (shown in FIG. 3C). In the speciation configuration300A, fluid received from the second valve 112 (e.g., diluted samplefluid held in the sample holding loop 120, eluent from an eluent sourcevia fluid line 122, etc.) can flow along flow path 302 through thespeciation bypass valve 300 and the speciation column 106 to the ICPtorch assembly 108 (with an injector 304 shown) for analysis by the ICPinstrument. In the speciation bypass configuration 300B, fluid receivedfrom the second valve 112 is not received in the speciation column 106and instead flows along flow path 306 to the ICP torch assembly 108(with an injector 304 shown) for analysis by the ICP instrument.

The dilution amount or ratio for inline dilution of a sample or standard(e.g. at the first valve 110, facilitated by the mixing portion) candepend on the species of interest to be analyzed. Referring to FIGS. 4Aand 4B, charts are provided showing arsenic detected over time by an ICPspectrometry system (e.g., system 100 described herein) for variousdilutions of apple juice samples (shown in FIG. 4A) and rice floursamples (shown in FIG. 4B). As shown, the effects of sample matrix onspecies elution are mitigated through sample dilution, where automateddilutions of 1 to 2, 1 to 3, 1 to 4, and 1 to 5 are provided. Inimplementations, for arsenic speciation, a five-fold dilution factor isutilized for separation of species of interest from apple juice and riceflour matrices.

In an example series of analyses, stable retention times were observedfor eighteen (18) separate samples spanning over ten different matricesover ten days of speciation testing. The samples included apple juice,wine, soft drinks, iced tea, and rice flour extract. Table 2 providesdata associated with the determined retention times.

TABLE 2 Retention Times (Seconds) Arsenobetaine DMA Arsenite MMAArsenate Average (All 93 117 157 240 263 Samples) Std. Deviation 0.8891.050 4.679 0.503 1.401 (All Samples) % RSD (All 1.0 0.9 3.0 0.2 0.5Samples)

In implementations, a calibration chromatogram can be generated by thesystem 100. For example, the system 100 can generate an auto-calibrationof a single mixed standard (5 parts per billion (ppb) of each species)and a calibration blank. Referring to FIG. 5, a calibration chromatogramis shown via auto-calibration by system 100 of inline dilution of fivearsenic species and a calibration blank. The dilutions include 50 partsper trillion (ppt), 100 ppt, 500 ppt, 1 ppb, and 5 ppb. Theauto-calibration of inline dilution of the arsenic standard via system100 resulted in highly linear calibration curves for all of the fivemajor arsenic species, as shown in FIG. 6.

Example 1

Analyses of five-fold diluted apple juice were performed via ICP-MS,with three different dilution methods: automatic inline dilution withdilution at of sample at time t=zero minutes, twenty minutes, fortyminutes, and sixty minutes, manual dilution with deionized water at timet=zero minutes, and manual dilution with mobile phase at time t=zerominutes. The results of arsenate (As(V)) detection for the automaticinline dilution method is shown in FIG. 7A; the results of arsenate(As(V)) detection for the manual dilution with deionized water is shownin FIG. 7B; and the results of arsenate (As(V)) detection for the manualdilution with mobile phase is shown in FIG. 7C. As shown, the detectedamounts of arsenate remained consistent over the sixty minute analysisfor the automatic inline dilution (e.g., FIG. 7A), whereas the detectedamounts of arsenate for each of the manual dilutions (e.g., FIGS. 7B and7C) increased over time. Referring to FIGS. 8A and 8B, the effects ofmanual dilution on three different apple juice concentrations can beseen. FIG. 8A shows the detected concentrations of arsenate (As(V)) foreach of the three apple juice samples for manual dilution (where allsamples are diluted at time t=zero) and for automated inline dilution(where samples are diluted at time t=zero minutes, twenty minutes, fortyminutes, and sixty minutes), including the percent difference in thedetected values. As can be seen, the percent difference between themanual and automated inline dilution methods includes a forty-onepercent difference, a six percent difference, and a forty-five percentdifference, where in all instances, the manual dilution samplesexhibited a higher detection of arsenate than the automatic inlinedilution samples. The total amount of measured arsenic (organic andinorganic species) is shown in FIG. 8B, as well as the detected amountsof arsenate (labeled 800) and the detected amounts of organic speciesand arsenite (As(III)) (labeled 802). As can be seen, the total amountof arsenic (labeled 804) measured remains the same between the manualdilution samples and the automatic inline samples, however the breakdownbetween the amounts of the detected species differs (e.g., 800 differsbetween manual dilution and automatic dilution samples; 802 differsbetween manual dilution and automatic dilution samples). In particular,the manual dilution samples all exhibit a higher detection of arsenate800 than the automatic inline dilution samples (as also shown in FIG.8A) and a lower detection of the remainder of arsenic species 802 (i.e.,the organic and arsenite species). While not being bound to any specificchemical conversion pathways, the organic species of arsenic couldconvert to arsenate when diluted and permitted to remain untested for aperiod of time (e.g., for up to sixty minutes in the example testsprovided herein above), thereby rendering an inaccurate analysis of theamounts of arsenic species present in the various samples. The automaticinline dilution provides nearly instantaneous dilution and sampling, sono substantial time is provided for the conversion of the arsenicspecies.

Referring to FIG. 9, a percent recovery of each of five major arsenicspecies provided during automatic inline dilution of apple juice andrice flour samples is shown, where all recoveries are within a (plus orminus) ten percent margin for both apple juice and rice flour extractionmatrices.

Example Implementations

In implementations, the system 100 can facilitate introduction of one ormore of a diluent, a standard, one or more eluents, a derivatizationfluid, or combinations thereof, prior to speciation, followingspeciation, or combinations thereof. For example, referring to FIGS. 10Athrough 10C, the valve system 104 of the system 100 includes the firstvalve 110, the second valve 112, and the speciation bypass valve 300.Referring to FIG. 10A, the first valve 110 is shown in a firstconfiguration to receive a sample 103 from sampling device 102 and tohold the received sample 103 in the holding loop 116. Each of the secondvalve 112 and the speciation bypass valve 300 is in a firstconfiguration to direct a flow of fluid (e.g., column rinse fluid,column preparation fluid, eluent, etc.) from the second valve 112 to thespeciation bypass valve 300, through the column 106, and out to thetorch assembly 108 (e.g., a nebulizer thereof).

Referring to FIG. 10B, the first valve 110 is switched to a secondconfiguration to introduce a carrier fluid (e.g., through a carrierfluid line 400 via action of the carrier syringe pump 118 b) to push thesample from the holding loop 116, whereby one or more of a diluent(e.g., supplied to the first valve 110 via a diluent line 402 to amixing port 404 via action of the diluent syringe pump 118 c) or astandard (e.g., supplied to the first valve 110 via a standard line 406to the mixing port 404 via action of the standard syringe pump 118 d) isintroduced to the sample at a mixing port 408. The sample (e.g., dilutedor spiked with standard or both) is introduced to the second valve 112(e.g., via transfer line 410) and into the sample holding loop 120.

Referring to FIG. 10C, the first valve 110 is switched to the firstconfiguration to rinse the holding loop 116. The second valve 112 isswitched to a second configuration to introduce an eluent (e.g., throughan eluent fluid line 412) to carry the sample from the sample holdingloop 120 to the speciation bypass valve 300 (e.g., via transfer line414) to direct the sample through the column 106 for speciation, and outto the torch assembly 108 (e.g., a nebulizer thereof). Inimplementations, the eluent is introduced to the second valve 112 viathe third valve 114 in fluid communication with one or more eluentsources where the eluent fluid line 412 is coupled between the secondvalve 112 and the third valve 114. An example chart of intensity overtime illustrating separation of arsenic species by the column 106 isshown in FIG. 10D. In implementations, the eluent fluid line 412 isfluidically coupled to a first eluent syringe pump to receive a firsteluent to facilitate separation of the species of interest of thesample, or a portion thereof. For example, the first eluent can beintroduced to the second valve 112 via the third valve 114 in fluidcommunication with the first eluent source through operation of thefirst eluent syringe pump, where the eluent fluid line 412 is coupledbetween the second valve 112 and the third valve 114. Introduction of asingle eluent to the column 106 permits isocratic elution methods, suchas for chromium speciation analysis. The second valve 112 can alsoreceive a second eluent (e.g., via a second eluent syringe pumpintroducing the second eluent via eluent fluid line 416 to introduce asecond eluent to the speciation bypass valve 300 (e.g., via transferline 414) to facilitate elution of the remainder of species retained bythe column 106 (e.g., after the first eluent passes through column 106for a first period of time). For example, the second eluent can beintroduced to the second valve 112 via the third valve 114 in fluidcommunication with the second eluent source through operation of thesecond eluent syringe pump, where the eluent fluid line 416 is coupledbetween the second valve 112 and the third valve 114. Multiple eluentswith separate syringe pump control can facilitate gradient elutionsthrough the column 106 (described further with respect to FIG. 14),where the first eluent can be introduced to the second valve 112 for afirst period of time followed by introduction of the second eluent tothe second valve 112 for a second period of time.

The system 100 can also facilitate introduction of additional fluids toa sample after the sample exits the column 106 and before the sample isintroduced to the torch assembly 108 or other component of the ICPinstrument. For example, in an implementation, the speciation bypassvalve 300 includes a fluid addition port 418 coupled to a fluid additionline 420 to receive a fluid into the speciation bypass valve 300 formixing with the sample after the sample exits the column 106. Forexample, the fluid addition line 420 can receive the additional fluidthrough pumping action of a third syringe pump that is operably coupledto a fluid source (e.g., a reagent bottle). The additional fluid caninclude, but is not limited to, a diluent, a standard, or aderivatization fluid. Introduction of a diluent following separation ofthe chemical species in the column 106 allows for post-column dilution,which can facilitate favorable column separation conditions, such as byutilizing certain concentrations of acids or salts, while avoidingsaturation of ICP-MS cones if the separation conditions are inefficientor detrimental for analysis by the ICP instrument. For example, for asample flow rate of 250 μL/min, a diluent can be added at a flow rate of250 μL/min to reduce the concentration of the sample by half just beforethe sample is introduced to the ICP instrument. Introduction of astandard following separation of the chemical species in the column 106allows for post-column standard checks, such as by providing a standardfor a fixed time period to provide an intermittent internal check, or byproviding a standard on a continuous basis to provide continuousoperation stability checks (e.g., to verify normal operating functionsof the system 100), or the like. Introduction of chemicals forderivatization following separation of the chemical species in thecolumn 106 allows formation of detectable complexes with otherwisedifficult-to-detect species to facilitate analysis of the species in theICP instrument. For example, barium can be introduced to the speciationbypass valve 300 to form a complex with fluorine detectable by the ICPinstrument. In implementations, the fluid introduced to the speciationbypass valve 300 via the fluid addition line 420 flows through the fluidaddition port 418 and through a fluid addition channel 422 to mix withthe sample leaving the column 106 at a mixing port 424 of the speciationbypass valve 300 before leaving the speciation bypass valve 300 to thetorch assembly 108 for analysis by the ICP instrument.

In implementations, the system 100 can bypass the column 106 to providea total metals analysis for the sample. For example, referring to FIGS.11A through 11C, the speciation bypass valve 300 is shown in a secondconfiguration to receive a fluid from the second valve 112 into areceiving port 426 of the speciation bypass valve 300 and to direct thefluid to an exit port 428, where the fluid leaves the speciation bypassvalve 300 and is directed to the torch assembly 108. Referring to FIG.11A, the first valve 110 is shown in the first configuration to receivea sample 103 from sampling device 102 and to hold the received sample103 in the holding loop 116. The second valve 112 is in the firstconfiguration to direct a fluid of fluid (e.g., rinse fluid, carrierfluid, eluent, etc.) from the second valve 112 to the speciation bypassvalve 300 (in the second configuration), bypassing the column 106, andout to the torch assembly 108 (e.g., a nebulizer thereof).

Referring to FIG. 11B, the first valve 110 is switched to the secondconfiguration to introduce a carrier fluid (e.g., through a carrierfluid line 400) to push the sample from the holding loop 116, wherebyone or more of a diluent (e.g., supplied to the first valve 110 via thediluent line 402 to the mixing port 404 via action of the diluentsyringe pump 118 c) or a standard (e.g., supplied to the first valve 110via the standard line 406 to the mixing port 404 via action of thestandard syringe pump 118 d) is introduced to the sample at a mixingport 408. The sample (e.g., diluted or spiked with standard or both) isintroduced to the second valve 112 (e.g., via transfer line 410) andinto the sample holding loop 120.

Referring to FIG. 11C, the first valve 110 is switched to the firstconfiguration to rinse the holding loop 116. The second valve 112 isswitched to the second configuration to introduce an eluent (e.g.,through an eluent fluid line 412) or other fluid to carry the samplefrom the sample holding loop 120 to the speciation bypass valve 300(e.g., via transfer line 414 to receiving port 426) to direct the sampleto the exit port 428, bypassing the column 106, and out to the torchassembly 108 (e.g., a nebulizer thereof). In implementations, the eluentis introduced to the second valve 112 via the third valve 114 in fluidcommunication with one or more eluent sources where the eluent fluidline 412 is coupled between the second valve 112 and the third valve114. An example chart of intensity over time illustrating total metalsanalysis of arsenic by the ICP instrument is shown in FIG. 11D.

In implementations, the valve system 104 includes the second valve 112and the speciation bypass valve 300 without the first valve 110. Forexample, referring to FIG. 12A, the second valve 112 is shown in thefirst configuration to receive a sample 103 from a sample source, suchas the sampling device 102 or another valve system configured to dilutethe sample, introduce standards to the sample, or combinations thereof,prior to introduction to the valve system 104, where the sample is heldin the holding loop 120. The speciation bypass valve 300 is shown in thefirst configuration to direct a flow of fluid (e.g., column rinse fluid,column preparation fluid, eluent, etc.) from the second valve 112 to thespeciation bypass valve 300, through the column 106, and out to thetorch assembly 108 (e.g., a nebulizer thereof).

Referring to FIG. 12B, the second valve 112 is switched to the secondconfiguration to introduce an eluent (e.g., through the eluent fluidline 412) to carry the sample from the sample holding loop 120 to thespeciation bypass valve 300 (e.g., via transfer line 414) to direct thesample through the column 106 for speciation, and out to the torchassembly 108 (e.g., a nebulizer thereof). In implementations, the eluentfluid line 412 is coupled to a first eluent syringe pump to receive afirst eluent to facilitate separation of the species of interest of thesample, or a portion thereof. For example, the first eluent can beintroduced to the second valve 112 via the third valve 114 in fluidcommunication with the first eluent source through operation of thefirst eluent syringe pump, where the eluent fluid line 412 is coupledbetween the second valve 112 and the third valve 114. Introduction of asingle eluent to the column 106 permits isocratic elution methods, suchas for chromium speciation analysis. The second valve 112 can alsoreceive a second eluent (e.g., via a second eluent syringe pumpintroducing the second eluent via eluent fluid line 416 to introduce asecond eluent to the speciation bypass valve 300 (e.g., via transferline 414) to facilitate elution of the remainder of species retained bythe column 106 (e.g., after the first eluent passes through column 106for a first period of time). Multiple eluents with separate syringe pumpcontrol can facilitate gradient elutions through the column 106(described further with respect to FIG. 14), where the first eluent canbe introduced to the second valve 112 for a first period of timefollowed by introduction of the second eluent to the second valve 112for a second period of time.

The system 100 can also facilitate introduction of additional fluids toa sample after the sample exits the column 106 with the valve system 104shown in FIGS. 12A and 12B. In an implementation, an example of which isshown in FIG. 12B, the speciation bypass valve 300 includes the fluidaddition port 418 coupled to the fluid addition line 420 to receive afluid into the speciation bypass valve 300 for mixing with the sampleafter the sample exits the column 106. For example, the fluid additionline 420 can receive the additional fluid through pumping action of athird syringe pump that is operably coupled to a fluid source (e.g., areagent bottle). The additional fluid can include, but is not limitedto, a diluent, a standard, or a derivatization fluid, as described withreference to FIG. 10C. In implementations, the fluid introduced to thespeciation bypass valve 300 via the fluid addition line 400 flowsthrough the fluid addition port 418 and through the fluid additionchannel 422 to mix with the sample leaving the column 106 at the mixingport 424 of the speciation bypass valve 300 before leaving thespeciation bypass valve 300 for analysis by the ICP instrument.

Referring to FIG. 13, an example system 500 is shown for providingspeciation of a sample with post-column fluid addition capabilities. Thesystem 500 is shown with the valve system 104 described with referenceto FIGS. 12A and 12B. The second valve 112 is in fluid communicationwith a first eluent 502 supplied to the second valve 112 via the eluentfluid line 412 through operation of a first syringe pump 504 of a pumpsystem 506. The second valve 112 is also shown to be in fluidcommunication with a second eluent 508 supplied to the second valve 112via the eluent fluid line 416 through operation of a second syringe pump510 of the pump system 506. The speciation bypass valve 300 is shown tobe in fluid communication with an internal standard 512 supplied to thespeciation bypass valve 300 through operation of a third syringe pump514 of the pump system 506. While the third syringe pump 514 isdescribed to supply the internal standard 512 to the speciation bypassvalve, the system 500 is not limited to supplying the internal standard512. For instance, the third syringe pump 514 can supply fluidsincluding but not limited to, the internal standard 512, a diluent, aderivatization fluid, or other fluid. Further, the pump system 506 canbe utilized to deliver one or more eluents and additional fluids to thevalve system 104 described with reference to FIGS. 10A through 10C and11A through 11C.

Referring to FIG. 14, a table illustrating syringe pump operatingconditions during speciation of a sample is shown in accordance withexample implementations of the present disclosure. The table shownprovides example operating conditions for the pump system 506, which inFIG. 14 is facilitating a gradient elution of a sample from the column106. For instance, for a first time period, t₁, the first syringe pump504 is directed to operate to provide a flow rate of 300 μL/min, thesecond syringe pump 510 is directed to operate to provide a flow rate of0 μL/min (or directed to remain idle or otherwise non-operational), andthe third syringe pump 514 is directed to operate to provide a flow rateof 50 μL/min such that 300 μL/min of the first eluent 502, 0 μL/min ofthe second eluent 508, and 50 μL/min of additional fluid (e.g., internalstandard 512) is introduced to the ICP instrument. For a second timeperiod, t₂, the first syringe pump 504 is directed to operate to providea flow rate of 0 μL/min (or directed to remain idle or otherwisenon-operational), the second syringe pump 510 is directed to operate toprovide a flow rate of 300 μL/min, and the third syringe pump 514 isdirected to operate to provide a flow rate of 50 μL/min such that 0μL/min of the first eluent 502, 300 μL/min of the second eluent 508, and50 μL/min of additional fluid (e.g., internal standard 512) isintroduced to the ICP instrument. The pump system 504 can be controlled,for example, by the computing system 150 described herein.

CONCLUSION

Although the subject matter has been described in language specific tostructural features and/or process operations, it is to be understoodthat the subject matter defined in the appended claims is notnecessarily limited to the specific features or acts described above.Rather, the specific features and acts described above are disclosed asexample forms of implementing the claims.

What is claimed is:
 1. A system comprising: a first valve, the firstvalve having a first valve configuration to receive a sample into aholding loop coupled to the first valve and a second valve configurationto transfer the sample from the holding loop out of the first valvethrough operation of a pump; and a second valve coupled to the firstvalve, the second valve having a first valve configuration configured toreceive the sample from the first valve and direct the sample to aspeciation column to separate one or more species of the sample fromrespective other species of the sample, the second valve furtherincluding a fluid addition port configured to receive a fluid into thesecond valve to mix with the sample after the sample exits thespeciation column, the second valve having a second valve configurationconfigured to receive the sample from the first valve and bypass thespeciation column while transferring the sample out of the second valve.2. The system of claim 1, wherein the second valve further includes amixing port configured to introduce the fluid received through the fluidaddition port to the sample.
 3. The system of claim 2, wherein thesecond valve further includes a channel fluidically coupling the fluidaddition port and the mixing port, the channel configured to introducethe fluid received through the fluid addition port to the mixing port.4. The system of claim 3, further comprising a pump fluidically coupledwith the fluid addition port to introduce the fluid to the second valve.5. The system of claim 4, wherein the pump fluidically coupled with thefluid addition port includes a syringe pump.
 6. The system of claim 1,wherein the fluid includes at least one of an internal standard, adiluent, or a derivatization fluid.
 7. The system of claim 1, whereinthe first valve further includes a first port configured to receive afirst eluent.
 8. The system of claim 7, further comprising a firsteluent pump in fluid communication with the first valve, the firsteluent pump operable to introduce the first eluent to the first portwhen the first valve is in the second configuration.
 9. The system ofclaim 7, wherein the first valve includes a second port configured toreceive a second eluent.
 10. The system of claim 9, further comprising asecond eluent pump in fluid communication with the first valve, thesecond eluent pump operable to introduce the second eluent to the secondport when the first valve is in the second configuration.
 11. The systemof claim 1, further comprising a third valve fluidically coupled to thefirst valve, wherein the first valve is fluidically coupled between thethird valve and the second valve, the third valve having a first valveconfiguration to receive the sample into a holding loop coupled to thethird valve and a second valve configuration to transfer the sample fromthe holding loop out of the third valve to the first valve.
 12. Thesystem of claim 11, wherein the third valve includes a first mixing portfluidically coupled to each of a first fluid line and a second fluidline, and wherein the first mixing port is fluidically coupled to asecond mixing port.
 13. The system of claim 12, wherein the secondmixing port is fluidically coupled to each of the first mixing port andthe holding loop coupled to the third valve when the third valve is inthe second valve configuration, and wherein the second mixing port isfluidically coupled to the first mixing port but not the holding loopwhen the third valve is in the first valve configuration.
 14. The systemof claim 1, wherein the second valve fluidically couples the first valveto a torch assembly when the second valve is in each of the first valveconfiguration and the second valve configuration.
 15. A systemcomprising: a first valve, the first valve having a first valveconfiguration to receive a sample into a holding loop coupled to thefirst valve and a second valve configuration to transfer the sample fromthe holding loop out of the first valve through operation of a pump; anda second valve coupled to the first valve, the second valve having afirst valve configuration configured to receive the sample from thefirst valve and direct the sample to a speciation column to separate oneor more species of the sample from respective other species of thesample and having a second valve configuration configured to receive thesample from the first valve and bypass the speciation column whiletransferring the sample out of the second valve, the second valvefurther including a fluid addition port configured to receive a fluidinto the second valve to mix with the sample after the sample exits thespeciation column, a mixing port configured to introduce the fluidreceived through the fluid addition port to the sample, and a channelfluidically coupling the fluid addition port and the mixing port, thechannel configured to introduce the fluid received through the fluidaddition port to the mixing port.
 16. The system of claim 15, furthercomprising a pump fluidically coupled with the fluid addition port tointroduce the fluid to the second valve.
 17. The system of claim 15,further comprising: a first eluent pump in fluid communication with afirst port the first valve, the first eluent pump operable to introducea first eluent to the first port when the first valve is in the secondconfiguration; and a second eluent pump in fluid communication with asecond port the first valve, the second eluent pump operable tointroduce a second eluent to the second port when the first valve is inthe second configuration.
 18. The system of claim 15, further comprisinga third valve fluidically coupled to the first valve, wherein the firstvalve is fluidically coupled between the third valve and the secondvalve, the third valve having a first valve configuration to receive thesample into a holding loop coupled to the third valve and a second valveconfiguration to transfer the sample from the holding loop out of thethird valve to the first valve.
 19. The system of claim 18, wherein thethird valve includes a first mixing port fluidically coupled to each ofa first fluid line and a second fluid line, wherein the first mixingport is fluidically coupled to a second mixing port, and wherein thesecond mixing port is fluidically coupled to each of the first mixingport and the holding loop coupled to the third valve when the thirdvalve is in the second valve configuration, and wherein the secondmixing port is fluidically coupled to the first mixing port but not theholding loop when the third valve is in the first valve configuration.20. The system of claim 15, wherein the second valve fluidically couplesthe first valve to a torch assembly when the second valve is in each ofthe first valve configuration and the second valve configuration.